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Compound Detail

CHEMBL5191783

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C[C@H]1C[C@@H](N2C(=N)N[C@](C)(c3cccc(Nc4ccc(C5CC5)nc4)c3Cl)CC2=O)CCO1

Basic Information

ChEMBL ID CHEMBL5191783
Phase Preclinical
Structure Type MOL
InChI Key NRQARCCHBBGTDO-LCAJTWGOSA-N
13
Targets
15
Activities
1
Assay Types
15
PK Parameters
16
Publications
0
Known Names

Molecular Properties

468.0
MW (Da)
4.90
ALogP
5
HBA
3
HBD
90.3
PSA (Ų)
0.58
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H30ClN5O2
MW 468.00
Aromatic Rings 2
Heavy Atoms 33
NP-Likeness -0.48

Activity Summary

IC50 15 meas. best 8.15

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasmepsin X
CHEMBL4523390
IC50 8.15 8.15 7.0 1
Unchecked
CHEMBL612545
IC50 8.15 6.725 7.0 2
Plasmodium falciparum
CHEMBL364
IC50 7.85 7.75 14.0 2
Cathepsin D
CHEMBL2581
IC50 7.19 7.19 64.0 1
Renin
CHEMBL286
IC50 6.75 6.75 180.0 1
Plasmepsin IX
CHEMBL5169236
IC50 6.6 6.6 250.0 1
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 5.3 5.3 5000.0 1
Potassium voltage-gated channel subfamily A member 5
CHEMBL4306
IC50 5.3 5.3 5000.0 1
Sodium channel protein type 8 subunit alpha
CHEMBL5202
IC50 5.1 5.1 8000.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.85 4.85 14000.0 1
HepG2
CHEMBL395
IC50 4.8 4.8 16000.0 1
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL1940
IC50 4.57 4.57 27000.0 1
A-type voltage-gated potassium channel KCND3
CHEMBL1964
IC50 4.55 4.55 28000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2.0 10^6nM Mus musculus
AUC 819.0 ng.hr.mL-1 Rattus norvegicus
AUC 1506.96 ng.hr.mL-1 Canis lupus familiaris
AUC 7675.2 ng.hr.mL-1 Rattus norvegicus
AUC 29109.6 ng.hr.mL-1 Canis lupus familiaris
CL 20.5 mL.min-1.kg-1 Rattus norvegicus
CL 7.28 mL.min-1.kg-1 Canis lupus familiaris
Cmax 736.0 nM Rattus norvegicus
Cmax 2730.0 nM Canis lupus familiaris
F 94.0 % Rattus norvegicus
F 193.0 % Canis lupus familiaris
T1/2 7.0 hr Rattus norvegicus
T1/2 20.0 hr Canis lupus familiaris
Tmax 8.0 hr Rattus norvegicus
Tmax 8.0 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasmepsin X IC50 = 7.0 nM 8.15 Inhibition of Plasmodium falciparum recombinant C-terminal TEV cleavable 8his-ta... 36216349
Unchecked IC50 = 7.0 nM 8.15 Inhibition of Plasmodium vivax PMX by FRET assay 36216349
Plasmodium falciparum IC50 = 14.0 nM 7.85 Antimalarial activity against asexual blood stage Plasmodium falciparum 3D7 asse... 36216349
Plasmodium falciparum IC50 = 22.5 nM 7.65 Antimalarial activity Plasmodium falciparum Dd2-B2 assessed as inhibition of par... 36216349
Cathepsin D IC50 = 64.0 nM 7.19 Inhibition of human cathepsin D 36216349
Renin IC50 = 180.0 nM 6.75 Inhibition of human renin 36216349
Plasmepsin IX IC50 = 250.0 nM 6.6 Inhibition of Plasmodium falciparum PMIX by FRET assay 36216349
Unchecked IC50 = 5000.0 nM 5.3 Inhibition of BACE (unknown origin) 36216349
Sodium channel protein type 5 subunit alpha IC50 = 5000.0 nM 5.3 Inhibition of NaV1.5 (unknown origin) cardiac ion channel by patch clamp assay 36216349
Potassium voltage-gated channel subfamily A member 5 IC50 = 5000.0 nM 5.3 Inhibition of Kv1.5 (unknown origin) by patch clamp method 36216349
Sodium channel protein type 8 subunit alpha IC50 = 8000.0 nM 5.1 Inhibition of NaV1.8 (unknown origin) cardiac ion channel by patch clamp assay 36216349
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 14000.0 nM 4.85 Inhibition of hERG cardiac ion channel by patch clamp assay 36216349
HepG2 IC50 = 16000.0 nM 4.8 Cytotoxicity against human HepG2 cells assessed reduction in cell viability 36216349
Voltage-dependent L-type calcium channel subunit alpha-1C IC50 = 27000.0 nM 4.57 Inhibition of Cav1.2 (unknown origin) cardiac ion channel by patch clamp assay 36216349
A-type voltage-gated potassium channel KCND3 IC50 = 28000.0 nM 4.55 Inhibition of Kv4.3 (unknown origin) by patch clamp method 36216349

Literature References

PubMed DOI Target Context # Activities
36216349 10.1021/acs.jmedchem.2c01336 ADMET 43
36216349 10.1021/acs.jmedchem.2c01336 Plasmodium falciparum 14
36216349 10.1021/acs.jmedchem.2c01336 No relevant target 7
36216349 10.1021/acs.jmedchem.2c01336 Plasmodium berghei 5
36216349 10.1021/acs.jmedchem.2c01336 Unchecked 3
36216349 10.1021/acs.jmedchem.2c01336 Plasmepsin X 2
36216349 10.1021/acs.jmedchem.2c01336 Plasmepsin IX 1
36216349 10.1021/acs.jmedchem.2c01336 Cathepsin D 1
36216349 10.1021/acs.jmedchem.2c01336 Renin 1
36216349 10.1021/acs.jmedchem.2c01336 HepG2 1
36216349 10.1021/acs.jmedchem.2c01336 Voltage-gated inwardly rectifying potassium channel KCNH2 1
36216349 10.1021/acs.jmedchem.2c01336 Sodium channel protein type 5 subunit alpha 1
36216349 10.1021/acs.jmedchem.2c01336 Sodium channel protein type 8 subunit alpha 1
36216349 10.1021/acs.jmedchem.2c01336 Voltage-dependent L-type calcium channel subunit alpha-1C 1
36216349 10.1021/acs.jmedchem.2c01336 Potassium voltage-gated channel subfamily A member 5 1
36216349 10.1021/acs.jmedchem.2c01336 A-type voltage-gated potassium channel KCND3 1

Data from ChEMBL 36 via Core Engine